systemsbiologyfandomcom-20200214-history
Systems Biology Wiki
Why it is important to consider the entire system. Introduction goes here. History Although it may seem as though the systems approach is a novel idea of the 20th/21st century, it actually is as ancient as science itself. Already, Aristotle (384-322 B.C.) stated ‘the whole is something over and above its parts and not just the sum of them’ i. However, in the 17th century a reductionist approach took hold of the developing science of biology. Although reductionisms and holism are often seen as opposites, there is a need to utilize both lines of approach and their ability to answer different questions in order to fully understand an organism ii. Systems analysis has historically been part of many biology areas, such as ecology, immunology and developmental biology. However, in molecular biology it was not necessary to use quantification and sophisticated mathematical models in order to understand how life works iii. The roots of systems biology lie in the holistic approach to organisms as a system developed in the 20th century. According to Denis Noble, Claude Bernard was the first system biologist iv. He developed the theory of the permanence of homeostasis (milieu intérieur) in the 1800, using an integrative approach to the cell. Some other pioneers were Norbert Wiener with the mathematical theory of communication and control of systems through regulatory feedback, i.e. cybernetics in 1948v, and Ludwig von Bertalanffy with the formulation of the general systems theory in 1969 vi. The action potential along neuronal axons was one of the first numerical simulations in biology, published in 1952 vii. In 1966 systems biology was formally launched at the international symposium in Cleveland, USA viii. The 60s and 70s then saw the development of analysis methods, such as metabolic control analysis, to study complex molecular systems. In the 90s, with the birth of functional genomics, systems biology started to undergo enormous expansion. The first quantitative model of the metabolism of a cell was published in 1999 ix. The completion of various genome projects and the large increase of data from the –omics, as well as advances in high-throughput experiments and bioinformatics pushed research forward and caused molecular biology to evolve into systems biology x (Fig. 1). The 21st century saw systems biology research centers opening around the world. In 2006 the National Science Foundation (NSF) put a grand challenge forward – to build a mathematical model of the whole cellxi. The rapid expansion of systems biology becomes clear when a PubMed search results in nearly 4,000 publications this year alone. x ---- i Aristotle (1946) ‘The Politics (translated’, E. Baker. Oxford, UK: Oxford University Press. ii Trewavas, A. (2006) ‘A Brief History of Systems Biology’, The Plant Cell, 18, pp. 2420-2430. iii Way, J.C., Silver, P.A. (2007) ‘Systems Enegineering Without an Engineer: Why We Need Systems Biology’, Wiley InterScience, 13(2), pp. 22-29. iv Saks, V., Monge, C., Guzun, R. (2009) ‘Philosophical Basis and Some Historical Aspects of Systems Biology: From Hegel to Noble – Applications for Bioenergetic Research’, Int. J. Mol. Sci., 10(3), pp. 1161-1192. v Wiener, N. (1948) ‘Cybernetics or the Control and Communication in The Animal and The Machine’, New York: John Wiley & Sons, Inc. vi Von Bertalanffy, L. (1969) ‘General Systems Theory: Foundations, Development, Applications’ New York: George Braziller Inc. vii Hodgkin, A.L., Huxley, A.F. (1952) ‘A quantitative description of membrane current and its application to conduction and excitation in nerve’, Journal of Physiology, 117(4), pp. 500-544. viii Mesarovic, M.D. (1968) ‘Systems Theory and Biology’, Berlin: Springer Verlag. ix Tomita, M., Hashimoto, K., Takahashi, K., Shimizu, T.S., Matsuzaki, Y., Miyoshi, F., Saito, K., Tanida, S., Yugi, K., Venter, J.C., Hutchinson Ill, C.A. (1999) ‘E-CELL: Software Environment for Whole Cell Simulation’, Bioinformatics 15(1), pp.72-84. x Westerhoff, H.V., Palsson, B.O. (2004) ‘The evolution of molecular biology into systems biology’, Nature Biotechnology, 22(10), pp. 1249-1252. xi Omenn, G.S. (2006) ‘Grand Challenges and Great Opportunities in Science, Technology and Public Policy’, Science, 341(5806), pp. 1696-1704. Associated Diciplines Joanne's stuff. Influence and Impact The importance of understanding an entire system is evident in the influence and impact systems biology has already had on understanding a variety of biological mechanisms, and in the quantity of developments resulting from research involving systems biology. Research based on understanding systems has impacted a wide range of scientific areas, some of which are described here: Modelling Systems Systems can be modelled and simulated on a number of levels: *Simulation of cellular processes within the cell *Simulation of cell development *Simulation of entire organs *Simulation of an entire organism1 An example of this is the simulation of signal transduction pathways, which often involve large numbers of molecules and a complex web of interactions and reactions. They can be studied computationally through the use of kinetic models: Reaction equations and parameters can be set, and the pathway can be simulated to analyse how it reacts to various stimuli2. Understanding Complex Diseases/Pathology Many diseases can be studied at a system level in order to better understand their mechanisms and how they progress. For example; cell shape in cancer can be studied using fractal analysis – irregular structures can be characterized and distinguished, such as differentiating between benign and malignant neoplasms3. Another example is metabolic syndrome: Systems biology can be used to study interactions between the genes involved, the environmental impact on such genes, and lipodomic profiles of plasma membranes4. Heart failure is another candidate for benefitting from a systems-based approach, as the numerous biochemical pathways and networks involved in each clinical phenotype of the condition can be identified5. Understanding Infectious Diseases Systems biology can be used to understand the numerous systems involved in infectious disease. In this case it is useful to understand the systems of the host and the pathogen. Understanding these can help to discover the pathogenesis of the infection, and can identify therapeutic targets. An example of this the use of haplo-insufficiency screens to select new drug targets to treat fungal infections6. Developing Biotechnology Understanding an entire system can identify niches in organisms that can be utilised in biotechnology. For example, metabolic flux analysis and complete genome sequencing has been used to study the metabolic pathways of Corynebacterium glutamicum, allowing development of its use in the production of amino acids7. Understanding plant systems through the use of systems biology can also unlock their potential in synthetic biology, for example the synthetic production of plant-derived compounds for pharmacological use8. Drug Development Another impact has been on drug development. Human genome sequencing has provided a base from which to develop personalised medicines, whilst the sequencing of microbial genomes presents scope for identification of novel drug targets to treat infectious disease1. Cancer signalling networks can be modelled and studied to develop new therapies. For example; modelling of the ErbB network recently identified ErbB3 as a drug target for cancer therapy. The research has led to development of a monoclonal antibody against ErbB3, which has reached phase II clinical trials9. In the field of anti-epileptic drugs, the “Systems Biology of Epilepsy Project” is combining numerous data types to identify genes expressed in seizure zones of the epileptic brain. These genes could be targets of future therapies10. References: 1. Yao, T. (2002) ‘Bioinformatics for the genomic sciences and towards systems biology. Japanese activities in the post-genome era’, Progress in Biophysics and Molecular Biology, 80(1-2), pp. 23-42. 2. Babu, C.V.S., Song, E.J. and Yoo, Y.S. (2006) ‘Modeling and simulation in signal transduction pathways: a systems biology approach’, Biochimie, 88(3-4), pp. 277-283. 3. Bizzam, M., Giuliani, A., Cucina, A., D’Anselmi, F., Soto, A.M. and Sonnenschein, C. (2011) ‘Tractal analysis in a systems biology approach to cancer’, Seminars in Cancer Biology, 21(3), pp. 175-182. 4. Orešič, M. (2010) ‘Systems biology strategy to study lipotoxicity and the metabolic syndrome’, Biochimica et Biophysica Acta (BBA) – Molecular and Cell Biology of Lipids, 1801(3), pp. 235-239. 5. Louridas, G.E. and Lourida, K.G. (2011) ‘A conceptual paradigm of heart failure and systems biology approach’, International Journal of Cardiology, In press, corrected proof 6. Santamaría, R., Rizzetto, L., Bromley, M., Zelante, T., Lee, W., Cavalieri, D., Romani, L., Miller, B., Gut, I., Santos, M., Pierre, P., Bowyer, P. And Kapushesky, M. (2011) ‘Systems biology of infectious diseases: a focus on fungal infections’, Immunobiology, 216(11), pp. 1212-1227. 7. Wendisch, V.F., Bott, M., Kalinowski, J., Oldiges, M. And Wiechert, W. (2006) ‘Emerging Corynebacterium glutamicum systems biology’, Journal of Biotechnology, 124(1), pp. 74-92. 8. Zurbriggen, M.D., Moor, A. And Weber, W. (2012) ‘Plant and bacterial systems biology as platform for plant synthetic bio(techno)logy’, Journal of Biotechnology, In press, corrected proof 9. Prasasya, R.D., Tian, D. And Kreeger, P.K. (2011) ‘Analysis of cancer signalling networks by systems biology to develop therapies’, Seminars in Cancer Biology, 21(3), pp. 200-26. 10. Margineanu, D.G. (2012) ‘Systems biology impact on antiepileptic drug discovery’, Epilepsy Research, 98(2-3), pp. 104-115. Future Outlook Craig's stuff. Category:Browse